We propose that nanofibrous/nanostructured PTFE prepared by a novel jet-blowing process will exhibit useful biomedical properties, especially for cardiovascular applications such as vascular grafts. [unreadable] A fundamental question to be answered in this study is whether nanoarchitecture at the same length scale as proteins will lead beneficial medical outcomes thus far inaccessible to conventional surface modification strategies. To answer this question we have formulated the following working hypotheses: (1) Because of the unique nanotopography/nanomorphology of polytetrafluoroethylene formed during the jet-blowing process, platelets will not adhere and become activated and anchorage-dependent mammalian cells such as endothelial cells will not adhere to these unmodified surfaces. (2) The surface of nanofibrous/nanostructured PTFE and related composites may be engineered/chemically functionalized to permit the selective adhesion of target cell types (e.g. endothelial cells) and development of appropriate phenotypic behavior. [unreadable] To test these hypotheses, the proposed research is divided into three specific aims directed toward the goal of developing unique nanostructured PTFE materials and composites capable of preventing the biofouling of medical devices. Because of the complex host-material interactions involved in vascular graft design, we will focus our efforts here on the study of endothelial cell proliferation on these materials since complete endothelialization of the lumen surface of a graft is highly desired. Issues related to in vivo platelet adhesion, complement activation, thrombogenesis, emboli formation will be the subject of future proposals (using the data gathered from this R21 as preliminary data). The research proposed here is of high risk, with little medical preliminary data describing the performance of these nanomaterials in cardiovascular applications. However, these nanomaterials may possess unique biomaterials properties resulting from their nanomorphology and designed surface functionalization and thus the reward may be high. [unreadable] This research will lead to improved medical devices, especially for treatment of cardiovascular disease. [unreadable] [unreadable] [unreadable]